Finland's first giant virus

A university compost heap has turned up Finland’s first documented “giant virus”. Gabriel Almeida, now at the Arctic University of Norway, had been collecting samples from all kinds of environments to try to find examples of one of these agents. These entities were first recognised for what they are - massive viruses bigger than bacteria in many cases - only about 20 years ago. Previously, scientists thought they were some strange form of bacterium. But they’ve since been detected in many different environments; they often have massive genomes, the workings of which we haven’t yet unpicked but which might surrender some useful secrets including recipes for novel antibiotics, and scientists think they might be evolutionarily extremely ancient, pointing us towards how early life might have operated. Now Finland can say it’s got one too!

Gabriel - This paper shows the isolation of the first giant virus in Finland. A giant virus is a virus which is larger than conventional viruses. What makes them giant are two things. One is their size itself, and they also have larger genomes. So it means that they code for more genes than most common viruses. And they are very commonly found in marine samples, in soil, and many other places, even in clinical samples. And this one we found, for example, came from a composting soil sample. So it means that they're really widespread.

Chris - It came from a compost heap?

Gabriel - Yeah.

Chris - And so did someone actually go, or did you go looking in a compost heap to find it? Or were you looking for something else and found this?

Gabriel - I was using a collection of samples in Finland. So I was collecting everything I could from lake water, from soil, from aquaculture-related samples. And we had this composting place in the university, and I collected a small amount of that. And then I tested it, and it was positive for the virus.

Chris - How did you actually test it? In other words, when you were just given this soil sample, how did you then flush the virus out?

Gabriel - Part of what makes giant viruses special is that most of them need to be eaten. So that's why we often use amoebae to isolate them, because the amoeba actively takes in food sources from the environment. And when they eat one of these viruses, they get infected. So the process is basically to take the sample, make it into a liquid form, and then mix that with a growing amoeba culture. The amoeba is going to eat everything that's in there. And if they find a virus and get sick, they die. And you can see that under the microscope – they’re dying, and we know that the likely virus is there.

Chris - When did it become apparent to you that you'd got one of these viruses? Was that because your amoeba culture became unwell, and you reasoned, well, something's killing it, it could be a virus?

Gabriel - Yeah, exactly. So from 24 to 48 hours later, plates where this sample was added were completely clear of amoebae. Everything died. And we just took a small amount of that to infect more amoebae, and we confirmed that it was killing the new batch. Then it's not too difficult to grow enough of the virus to extract DNA, the genomes, and sequence that. And once you know the DNA sequence, you can be sure that it's a virus and also which virus it is.

Chris - And was it the genome that gave you the clue that you’d got a new one, and that it was Finland’s first?

Gabriel - Yeah, exactly. So when we got the full genome sequence, we could see that it was a virus. We also discovered it was related to other known giant viruses. Then we were able to check the genes in detail and see their peculiarities and be sure that we had a new one in Finland.

Chris - Did you image it? So have you only interrogated it genetically, or have you actually been able to see it now?

Gabriel - So I actually did a lot of imaging as well, based on electron microscopy. And a big part of this paper was actually the cryo-electron microscopy imaging. After taking images of thousands of these viral particles, we constructed the structure in very fine detail to determine how the virus is built. That’s important for knowing how it stays stable in the environment and also how the proteins interact to protect the DNA and keep it viable for a while.

Chris - What does it look like and how big is it?

Gabriel - It's around 200 nanometres. Among the giant viruses, this is a small one. I have some which are five times larger than that.

Chris - Yeah, indeed. I mean, that would be about twice the size of a flu virus, wouldn’t it? Or twice the size of a coronavirus that causes COVID-19. It’d be about twice as big as that.

Gabriel - Exactly.

Chris - And in terms of its genetic code, how big is it?

Gabriel - It has 360,000 bases. In comparison, that's about 10 times larger than a phage, for example. Much more than corona – around 10 times larger than that as well. Out of all these bases, it codes for almost 400 genes.

Chris - Well, that’s quite a lot, isn’t it? I mean, if we take, say, chickenpox or the herpes virus that gives you cold sores, that’s got a fraction – a quarter – of that number of genes. That’s a lot.

Gabriel - Exactly. And what I find interesting is that it contains genes found only on this virus. So three out of these 388 genes are unique to this isolate. And we don’t know what they do. So we could have some surprises there. And anyway, 67% of these genes are hypothetical. We know they code for something, but we don’t know their function. So there’s huge biotechnological potential here to explore.

Chris - Why do they have such massive genomes? Do we actually see all of these genes working? Are they genes that are absolutely critical to the virus lifecycle?

Gabriel - No, they have a lot of accessory genes. And as mentioned, we don’t know about most of them. But it has been shown in the literature that some can bring new traits to the host. Some might hint at metabolic pathways that they may make the host express. And we have some theories that they use these genes to compete for the organisms when infecting the amoeba.

Chris - And have you watched them replicating? Can you see where inside the amoeba they grow? Do they go into the genetic material like a herpes virus? Or do they grow in the cytoplasm, a bit like a monkeypox virus or smallpox?

Gabriel - Yeah, we were able to see that. They get taken in by the amoeba, and their replication is in the cytoplasm. They don’t enter the nucleus. They tend to form viral factories – these big electron-dense masses inside the cell where the particles are produced. And for this virus species in particular, they also tend to form vesicles containing several viruses inside the cell. That’s important because when the cell dies, these vesicles form clusters of viruses in the environment. And it makes it easier for new amoebae to find and eat them to become infected.

Chris - It’s a fascinating phenomenon, though, isn’t it? Thinking big, why do you think these things even exist? And where do we think they came from in the first place? How did they evolve? Because they don’t seem to bear much resemblance to much else.

Gabriel - They are likely very ancient. When you check the DNA sequences from the environment, you find them everywhere – including at deep sea vents, for example, where life likely originated. So at least some branches of this group of viruses might be as old as life itself.

Chris - Is there anything we could use them for? Apart from the fact they’re academically fascinating, and there may well be some unusual biology locked up in those genes that we can slowly uncover. Do they have any applications that we could exploit?

Gabriel - Yes, for sure. We have lines of work here in Norway now trying to untap these hypothetical genes and see how they can be used in biotechnology. One area of investigation is whether some of the genes are used by the virus to kill bacteria. If that’s the case, then you might have something like a viral antibiotic that could be applied in clinics.